Kerkvliet N I, Steppan L B, Brauner J A, Deyo J A, Henderson M C, Tomar R S, Buhler D R
College of Veterinary Medicine, Oregon State University, Corvallis 97331.
Toxicol Appl Pharmacol. 1990 Aug;105(1):26-36. doi: 10.1016/0041-008x(90)90356-y.
There are conflicting reports in the literature regarding the role of the Ah locus in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) immunotoxicity. The present studies have utilized two congenic strains of C57Bl/6 mice that differ only at this locus to assess its influence on TCDD-induced suppression of antibody responses. Mice were given a single oral dose of TCDD 2 days prior to challenge with sheep red blood cells (SRBC) or trinitrophenyl-lipopolysaccharide (TNP-LPS). The subsequent dose-dependent effects of TCDD on the amount of antibody produced by splenic plasma cells were measured using the hemolytic antibody isotope release assay. In addition, the relative importance of the Ah genotype of lymphoid versus nonlymphoid tissue was examined in adoptive transfer experiments. Aryl hydrocarbon hydroxylase (AHH) activity was significantly induced in Ahbb mice by a dose of 0.5 micrograms/kg TCDD and maximally induced by a dose of 2 micrograms/kg. Ahdd mice required 10-fold higher doses of TCDD to induce comparable levels of AHH. The degree of thymic involution and liver hypertrophy induced by TCDD was also influenced by the Ah genotype of the animals. Both Ahbb and Ahdd mice exhibited dose-dependent suppression of the anti-TNP response following TCDD exposure. The ID50 was 7.0 micrograms/kg in Ahbb mice and 30.8 micrograms/kg in Ahdd mice. Suppression of the antibody response to SRBC was also dependent on the Ah locus. The ID50 in Ahbb mice was 0.6 micrograms/kg TCDD. However, an apparent biphasic dose response for suppression of the anti-SRBC response in Ahdd mice suggested the involvement of an Ah-independent component of suppression as well. In adoptive transfer studies, lymphocytes were identified as an Ah-dependent component of the response. The Ah-independent component of the response was not identified, and could be either lymphoid or nonlymphoid in nature. The possibility that T helper cells represent the Ah-independent component is discussed.
关于芳香烃受体（Ah）位点在2,3,7,8-四氯二苯并对二恶英（TCDD）免疫毒性中的作用，文献中有相互矛盾的报道。本研究利用了两种仅在该位点存在差异的C57Bl/6小鼠同基因品系，以评估其对TCDD诱导的抗体反应抑制的影响。在用绵羊红细胞（SRBC）或三硝基苯基脂多糖（TNP-LPS）攻击前2天，给小鼠单次口服TCDD。使用溶血抗体同位素释放试验测量TCDD对脾浆细胞产生抗体量的后续剂量依赖性影响。此外，在过继转移实验中研究了淋巴组织与非淋巴组织的Ah基因型的相对重要性。剂量为0.5微克/千克的TCDD可显著诱导Ahbb小鼠的芳烃羟化酶（AHH）活性，剂量为2微克/千克时诱导程度最大。Ahdd小鼠需要高10倍剂量的TCDD才能诱导出相当水平的AHH。TCDD诱导的胸腺退化和肝脏肥大程度也受动物Ah基因型的影响。TCDD暴露后，Ahbb和Ahdd小鼠均表现出抗TNP反应的剂量依赖性抑制。Ahbb小鼠的半数抑制剂量（ID50）为7.0微克/千克，Ahdd小鼠为30.8微克/千克。对SRBC抗体反应的抑制也取决于Ah位点。Ahbb小鼠的ID50为0.6微克/千克TCDD。然而，Ahdd小鼠抗SRBC反应抑制的明显双相剂量反应表明也涉及非Ah依赖性抑制成分。在过继转移研究中，淋巴细胞被确定为反应的Ah依赖性成分。未确定反应的非Ah依赖性成分，其性质可能是淋巴样或非淋巴样。讨论了辅助性T细胞代表非Ah依赖性成分的可能性。
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